Catalytic, Enantioselective Sulfenofunctionalization of Alkenes: Development and Recent Advances.

The last decade has witnessed a burgeoning of new methods for the enantioselective vicinal difunctionalization of alkenes initiated by electrophilic sulfenyl group transfer. The addition of sulfenium ions to alkenes results in the generation of chiral, non-racemic thiiranium ions. These highly reactive intermediates are susceptible to attack by a myriad of nucleophiles in a stereospecific ring-opening event to afford anti 1,2-sulfenofunctionalized products. The practical application of sulfenium ion transfer has been enabled by advances in the field of Lewis base catalysis. This Review will chronicle the initial discovery and characterization of thiiranium ion intermediates followed by the determination of their configurational stability and the challenges of developing enantioselective variants. Once the framework for the reactivity and stability of thiiranium ions has been established, a critical analysis of pioneering studies will be presented. Finally, a comprehensive discussion of modern synthetic applications will be categorized around the type of nucleophile employed for sulfenofunctionalization.

Enantioselective, Lewis Base-Catalyzed Carbosulfenylation of Alkenylboronates by 1,2-Boronate Migration.

A catalytic, enantioselective method for the preparation of chiral, non-racemic, alkylboronic esters bearing two vicinal stereogenic centers is described. The reaction proceeds via a 1,2-migration of a zwitterionic thiiranium-boronate complex to give exclusively anti carbosulfenylation products. A broad scope of aryl groups migrate with good yield and excellent enantioselectivity (up to 99:1 e.r.). Similarly, a range of di- and trisubstituted alkenylboronic esters are competent reaction partners. This method provides access to both secondary and tertiary chiral alkylboronic esters.

Enantioselective Synthesis of γ-Lactams by Lewis Base Catalyzed Sulfenoamidation of Alkenes.

A method for the catalytic, enantioselective, intramolecular 1,2-sulfenoamidation of alkenes is described. Lewis base activation of a suitable sulfur electrophile generates an enantioenriched, thiiranium ion intermediate from a ß,γ-unsaturated sulfonyl carboxamide. This intermediate is subsequently intercepted by the sulfonamide nitrogen resulting in cyclization to form γ-lactams. Electron-poor alkenes required the use of a new selenophosphoramidate Lewis base catalyst. Subsequent manipulations of the products harness the latent reactivity of both the amide and thioether functionality.